Low 'normal' B12 and high folate - B12 deficient?

I am new here. I have recently developed neurological symptoms (pins and needles, numbness, cold sensations), particularly in my hands and feet, although occasionally in other parts of my body such as legs. I am a vegetarian who eats dairy products and I have Rheumatoid Arthritis and take weekly folic acid supplements as I have been on methotrexate for over 20 years. I have other symptoms such as IBS, constant UTIs, psoriasis on my scalp (and sores in my nasal cavity) and a slightly sore tongue, which made me think I possibly had B12 deficiency, although no-one in my family has pernicious anaemia. I had a blood test last week which shows a B12 serum level of 228.0 ng/L (i.e. normal range), a serum folate level of 8.40 ug/L (i.e. high), a haemoglobin concentration of 111 g/L (i.e. low) and an MCV of 78.7fL (i.e. low).

My GP agreed to prescribe hydroxocobalamin injections (5 doses on alternate days, then one every 3 months); but do you think this sounds like B12 deficiency, and, if so, should I be having more injections until symptoms improve, as per NICE guidelines? Also, how soon would the injections begin to take affect? I think my neurological symptoms have improved since being on the injections (4 so far), although now I am tired at the end of the working week, they seem to 'kick off' again.

I have not had the Serum MMA or Homocysteine blood tests, as I have already started the B12 injections and apparently this can affect the result and deliver a 'false normal'.

I would appreciate any advice or guidance about this (sorry my post is so long!).

30 Replies

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  • Hi rebs48 I think your doctor is treating you appropriately for a B12 deficiency possibly caused by your vegetarian diet.

    Only you will know whether you need additional injections after the loading doses and that will depend on whether your symptoms are still present.

    It is not uncommon for some symptoms to appear to get worse before they get better as the B12 repairs the damage done to your system. As to how long this will take will depend on the length and severity of the deficiency - no two people are the same.

    I wish you well

  • Thanks, clivealive.

  • Hi rebs48

    Your B12 levels are just inside "normal" ranges but realistically pretty low and it is good your doctor has begun treating you for low B12. The following paper gives the BSH guidelines for treating B12 deficiency / Pernicious anaemia. As you have neurological symptoms you should really be treated with injections on alternate days until no further improvement then injections every 2 months.



    Have you been tested for anti-intrinsic factor antibodies to see if you have pernicious anaemia? Whatever the reason for your low B12 you ideally need it to be a whole load higher!

    Your MCV and haemaglobin are low. Have you had your iron levels checked too? Not sure if these are low due to your methotroxate treatment or if you may possibly be iron deficient anaemic too.

    Not sure what the normal range for folate results is in your area but this does not seem to be overly high, though probably within the normal range. Not sure what this should be for someone on methotrexate treatment, sorry. Methotrexate is a competitive inhibitor of DHFR (one of the folate cycle enzymes) hence why you are on what I imagine are high dose Folic acid tablets. I think the MTX mentioned on this diagram is methotrexate.


    Also not sure what effect being on methotrexate would have on homocysteine and MMA levels either, sorry.

    Some of your symptoms overlap with those of Folate deficiency so it may be hard to differentiate between a B12 deficiency and any side effects arising as a consequence of methotrexate treatment.

    There are loads of helpful links in the pinned posts on the RHS when you log on (or to the right of this thread) if you are on a PC or down at the bottom if you are on a mobile.

  • Thanks for such a detailed reply, taka. I'll take a look at the links.

  • Hi Rebs48. Hello and Welcome. First yes, this does sound like vitamin B12 deficiency. As clivealive says, B12 deficiency can be sometimes be caused by a vegetarian diet I think the fact that you are taking methotrexate complicates the picture. Here's what two commentators in the New England Journal of Medicine say about Methotrexate:

    'Weinblatt discussed the use of methotrexate for chronic diseases in adults (Feb. 2 issue).1 Although folic acid is helpful in reducing the toxic effects of methotrexate therapy,2 its expanded use may have an unintended consequence.

    In large doses, folic acid can correct the megaloblastic anemia associated with vitamin B12deficiency without correcting β€” and potentially even aggravating β€” the neurologic abnormalities associated with this deficiency.3 The coexistence of vitamin B12 deficiency and rheumatoid arthritis has been reported.4 In patients with Crohn's disease and ileal involvement, vitamin B12 deficiency is not uncommon.5

    With the increased use of methotrexate for various chronic diseases, there may be a greater likelihood that vitamin B12 deficiency will be masked. Such a deficiency should be considered in patients receiving methotrexate who have paresthesia, generalized weakness, gait disorders, or polyneuropathy. It may even be reasonable to screen all patients for concomitant vitamin B12deficiency at the start of methotrexate therapy'.

    Robert A. Fogari, M.D.

    Susan Hoch, M.D.

    Hahnemann University, Philadelphia, PA 19102-1192

    So..(and please excuse me I'm short of time so will have to be necessarily brief - but I'm sure others will comment too πŸ˜„)...

    A serum B12 level below 500 can result in B12 deficency with neurological symptoms - this can present without having macrocytic (large) red blood cells or a positive PA test result. And the methotrexate may well 'mask' macrocytic anaemia (what your GP may - mistakenly - be looking for as the only sign of B12 deficency - it's not.

    The low haemaglobin concentration and low MCV are indicative of iron deficency anaemia. Ask your GP to check your ferritin levels - these need to be in the middle of the range for optimum effect.

    Iron deficency anaemia will result in microcytic (small redblood cells) - this alters and reduces the size of the cells - and can also mask macrocytic anaemia.

    Also - people with absorption problems (which is likely in your case) also have other deficencies. Ask your GP to test vitamin D and magnesium.

    Doctors often say results are 'normal' when they're not. It's where the result sits in the reference range that's important. Get copies of your blood results and post them here, together with reference ranges for help with interpretation.

    You have one autoimmune condition (RA) so you are likely to have others - pernicious anaemia, for instance. Ask your GP to test anti-IF antibodies. If positve you definately have PA, if negative the accuracy rate is only 50% - you could still have PA (this is called antibody negative PA) - most GP's have never heard of this.

    And yes, you're correct - you should be on the intensive regime of B12 treatment because of your neurological symptoms.

    I'm going to put some links in at the end of this reply that will tell you the vital things you need to know about B12 deficency and / or PA (it's worth saying that the treatment for both is the same: B12 injections). The information will help you approach tour GP and persuade him to treat you in line with the guidelines. Hilighted the ' its' that are relevant to your case and go through them with him.

    It has to be said that GP's are very ill-informed about B12 deficency and PA so you may have to persevere and be persuasive.

    About recovery - the key here is getting enough B12 to effect proper neurological repair. It's quite difficult to say how quickly recovery will take place - for some it's quite quick, for others it takes a little longer - the key here is getting enough B12 injections to get and keep well. If symptoms return before the next injection is due this is a sure indicator that more frequent injections are required.

    Pleas keep in mind...GP's often insist on trying serum B12 levels rather than symtpoms. Wrong. All the guidelines state treat the symtpoms, not the blood results.

    Apologies...have to dash...just wanted to get something to you. You've come to the right place for help and support....lots of knowledgeable folks who will pop along to help πŸ˜„.

    Post any questions....and let us know how it goes.

    Good luck πŸ‘

    evidence.nhs.uk/formulary/b... (BNF B12 Deficiency: Hydroxocobalamin Treatment Regimes)

    pernicious-anaemia-society.... (PAS Symptom Checklist)

    stichtingb12tekort.nl/weten... (BSH B12 Deficiency / PA Diagnostic Flowchart)

    onlinelibrary.wiley.com/doi... (British Society Haematology (BSH) Guidelines: Treatment of B12 Deficiency and Folate Disorders)

    onlinelibrary.wiley.com/doi... (UKNEQAS B12 Treatment Alert)

    stichtingb12tekort.nl/weten... (Problems with Serum B12 Test)

    stichtingb12tekort.nl/weten... (Testing B12 During Treatment)

    stichtingb12tekort.nl/weten... (Misconceptions About B12 Deficiency – Good to know before seeing GP)

    stichtingb12tekort.nl/weten... (B12 Treatment Safety / Long Term Treatment for neurological symptoms)

    stichtingb12tekort.nl/weten... (B12 Deficiency & Neurological Symptoms: Can Present Without Macrocytosis or Pernicious Anaemia)


    P.s. You're right about the MMA and homocysteine...here's another link:

    stichtingb12tekort.nl/weten... (Methylmalonic Acid – MMA)

  • Foggyme - that is such a helpful, kind and informative reply. I now realise the picture is more complicated by being treated for another auto-immune disease (RA), taking folic acid supplements and having iron-deficiency anaemia. I will post the copy of my blood results here, in case I have missed something.

  • Foggyme (and any others) - here is a copy of my full blood test results from last week (before I started the cobalamin injections). Would these results fit with B12 deficiency? (NB I have been taking 5mg folic acid supplements weekly for over 15 years to counteract the methotrexate @ 7.5mg weekly):

    Total white blood count 10.3 10*9/L [3.9 - 10.2]

    Red blood cell count 4.30 10*12/L [3.9 - 5.2]

    Haemoglobin concentration 111 g/L [120.0 - 156.0]

    Haematocrit 0.340 L/L [0.355 - 0.455]

    Mean cell volume 78.7 fL [80.0 - 99.0]

    Mean cell haemoglobin level 25.8 pg [27.0 - 33.5]

    Red blood cell distribution width 15.4 % [11.0 - 16.0]

    Platelet count - observation 192 10*9/L [150.0 - 370.0]

    Plateletcrit 0.160

    Mean platelet volume 8.6 fL

    Neutrophil count 7.89 10*9/L [1.5 - 7.7]

    Lymphocyte count 1.55 10*9/L [1.1 - 4.5]

    Monocyte count - observation 0.56 10*9/L [0.1 - 0.9]

    Eosinophil count - observation 0.08 10*9/L [0.02 - 0.5]

    Basophil count 0.04 10*9/L [0.0 - 0.2]

    Erythrocyte sedimentation rate 30 mm [3.0 - 9.0]

    Serum vitamin B12 level 228.0 ng/L [211.0 - 911.0]

    Serum TSH level 1.67 mU/L [0.35 - 5.5]

    Serum folate level 8.40 ug/L [> 5.38]

    Thanks for any advice!

  • rebs48 - you can mention someone by typing @ followed by the name and when their name comes up clicking on it - this should send them a message - but otherwise they may not see the reply.

    Foggyme, taka and clivealive - rebs48 has posted blood results - definite signs of iron based anaemia in the results - folate levels bit non-descript - suspect they are actually on the low side which would fit with the methotrexate

    would have suggested trying to clarify B12 with MMA (homocysteine might be inconclusive as problems with folate would have raised levels) prior to start of treatment but that boat has probably sailed.

  • Hi rebs48. Yes...I agree with Gambit62.

    Low haemoglobin, haemocrit, haemaglobin concentration and MCV indicative of iron deficency anaemia. RCDW towards the high end supports this (can also indicate folate and/or vitamin D deficency).

    Also - your ESR is raised - indicative of inflammation - your RA perhaps?

    B12 is in what's called the 'grey' zone - within so called 'normal' limits but low enough to cause symtpoms of B12 deficency with neurological symtpoms (GP may not know this - as per perevious reply).

    And while I think about it, here's the link to the information about methotrexate, folate, B12 and PA from earlier posts. You might want to do a screen shot for your GP - they're often quite dismissive of what they call 'stuff on the Internet' so it'll be useful for you to be able to demonstrate a reliable source:



  • Yep, what they ^^^^ said! :-)

    If your doctor is going to check your iron levels it may be a good idea to not just rely on testing ferritin as this can be raised due to RA, even when your iron levels are low. Checking some of the other iron tests eg serum iron and total iron binding capacity etc would give a clearer idea of what is going on.

  • taka Gambit62 Foggyme, thanks for the helpful responses to my blood test results. My rheumatologist has booked an MRi scan for my neck as this is also affected by RA although this would not explain the pins and needles in the feet and legs. Would this show a sub-acute combined degeneration of the spinal cord?

  • Hi rebs48...you'd need MRI of whole spine to show SCDPC...perhaps your rheumatologist would consider organising it?


  • Thanks, Foggyme and taka , I'll speak to the GP and maybe ask the consultant to arrange this, just in case. It may show in the cervical spine results anyway.

  • Erm not sure to be honest - I know very little about MRIs, sorry (I'm not a medic). :-( Sub acute combined degeneration of the spinal cord seems to occur in the cervical and / or thoracic spine so I guess if they are looking at the neck (cervical spine) there is a chance it may show up if present. Maybe ask your rheumatologist if this scan would also pick it up? Sorry I'm not much help.

  • Apologies, Foggyme and taka , for all my questions and thanks for your patience (I'm new to this!). I read a couple of your replies on other posts which were useful. I am currently on a regime receiving 1mg cobalamin on alternate days (5 x 1mg in total) before 1 x 1mg every 3 months. What is the correct regime of B12 injections for B12 deficiency with neurological symptoms? In one of the posts, you said 5 mg (5 x 1mg) on alternate days before improvements, then 1mg every 2 months. Should I be asking my GP for this? I should have had the MMA blood test before I started the B12 injections, but my GP seemed to think I should have the IFA blood test (not MMA or Homocysteine) and this could be taken any time. Also, should I ask to have iron (ferritin) tablets, as well as the folic acid supplements for maximum efficacy?

  • Hi rebs48.

    The neurological regime is 6 x 1mg hydroxocobalamin on alternate days (the loading doses) then 1mg every other day until no further improvement (for up to two years) then 1mg every eight weeks). Has to be said though that every eight weeks is not enough for some people for the long term - but think about that later - just focus on getting the neurological regime for now. So yes, this is what you should be having.

    Note - your GP may say ah ha, but you don't have macrocytic anaemia (what he'll expect to see in PA) - well, your iron deficency anaemia will reduce the size of red blood cells so the large cells associated with macrocytic anaemia will be changed by this - made smaller. Also your GP may be unaware that B12 deficency with neurological symptoms can present without macrocytic anaemia and without a positive PA (anti-IF antibodies) test.

    Your GP is not quite right - while the anti-IF antibody test is the test for PA (which you should have) MMA and homocysteine levels will be raised in the presence of B12 and / or folate deficency and are often used when B12 results appear 'normal' to ascertain if a B12 deficency exists. In your case this would have been very useful since your GP may argue that as your levels are in the 'normal' reference range, you don't have B12 deficency. This of course is wrong (see replies above) so you may have to go prepared to present your case, with evidence, to get the right treatment (the link I gave in the first mail will provide all the evidence you need to do this).

    Be aware - the anti-IF antibody test is a quote unreliable test (but nothing better exists). If it's positve, you definately have PA. If it's negative it's only 50% accurate, so you could still have PA - this is called antibody negative PA - and you GP has most likely never heard of it (see the diagnostic flow chart in my first reply).

    It's also worth noting that B12 deficency can have causes other than PA, though your GP may not know this. The treatment for PA and / or B12 deficency (whatever the cause) is the same: B12 injections. And the golden rule is - and all the guidelines state - treat the symptoms, not the blood results. You have neurological symptoms associated with B12 deficency, you need the neurological regime of injections - even if you test so called negative for PA.

    And yes, you need a three month course of iron tablets to address your iron deficency anaemia. And as taka says above, it would be a good idea to ask your GP to do a full iron panel to assess true iron status. It's possible to have low ferritin (the protein that binds iron for absorption) but still have high iron levels in the blood, which could potentially cause iron overload - which would not be good. Ideally, your GP should do this both before iron supplementation and then again three months after the course of iron supplements.

    Have to say, B12 deficency and / or PA are quote complex conditions so please don't worry about asking questions. All here started where you are (we Admin's included) so can well remember how confusing and frightening it was (still is sometimes), especially when GP's are so ill-informed and often fail to diagnose and treat us deficients properly.

    So ask and post away...lot of lovely knowledgable folks in the forum who will always pop in to help.

    Good luck and let's know how you get on πŸ‘

  • Excellent reply, Foggyme, thanks so much to you and others for your helpful advice, which is particularly important when I am feeling a bit apprehensive and vulnerable. I'm going to the GP's tomorrow morning, armed with this useful information. I will let you know how I get on.

  • No problem rebs48...good luck...will await incoming...πŸ‘

  • Good luck with the GP rebs48! :-)

  • Just got back from the GP who has been very supportive. Having read the patient.info print-out I gave him (!), he agrees that there is a grey area for B12 deficiency with RA, methotrexate, folic acid supplements and iron deficiency anaemia complicating my blood results, with the result that we are continuing my B12 injections on alternate days for a further fortnight before another review appointment with him. I will also have a blood test for my ferritin levels, folate levels, another full blood count, TSH and T4 (to check for hyper- or hypothyroidism), ESR as it was raised (plus CRP), and magnesium and Vitamin D as Foggyme suggested. He also is requesting an IFA test, but is aware that this will be affected by the B12 injections and also I could be in the 25% who have sero-negative PA. I mentioned the homocysteine test, but he didn't go with it and hadn't heard of the active B12 test. We both think that the initial symptoms of paraesthesia in my left hand with pains in neck and shoulder could be a separate RA-related cervical spine nerve root issue as I am still having pain in that area, although the pins and needles elsewhere have improved substantially after the B12 injections. He is also writing to the Rheumatologist as he thinks they should organise some neurological tests for me. So some progress, although no official diagnosis which I would prefer. Maybe I will never get a diagnosis if I am a 'grey area' patient.

    Thanks to everyone for your advice and guidance as it made me more confident in the surgery. I am very lucky to have a really good GP who actually listens too.

  • Hi rebs48. That's great news πŸ˜„.

    Sounds like you've got a really good GP - and going prepared helped πŸ˜„. You'll be the envy of the whole forum πŸ™ƒ

    Hope everything continues to go in the right direction and that you begin to feel better very soon.

    Let us know how you get on and post again if you need any more help...or just for a chat...


  • Sounds like you've got a very helpful GP! :-) Hopefully some of the tests will help to work out what is going on.

  • I'm not sure whether my B12 injections are working any more, as last week I felt much better after just 3 injections (hardly any pins and needles), and now after 6 injections, my pins and needles have returned (although more reduced than before the treatment). Is this normal, Foggyme and taka or maybe I am just not B12 deficient after all? Also, I am due my IFA blood test tomorrow before my next B12 injection tomorrow - would it be better to wait until Monday to have the IFA, i.e., 3 days rather than 2 days before the B12, as I don't want my injections to affect the results?

  • Hi rebs48. People here often report that symptoms can feel,worse before they feel better. Nobody really knows why but the thinking is that it's to do with the nerves 'waking-up', receiving stronger signals, and the brain having to re-learn how to interpret those stronger signals. So what you're experiencing is not unusual. The fact that your pins and needles are reduced is good news and nerve repair does take longer that some of the other symptom relief obtained after treatment with B12. And it's quite early on in your treatment...so bear with it and don't get too dispirited πŸ˜„.

    About the IF test - best to leave a gap of one week following a B12 injection to avoid potentially skewing the results.

    So...keep jabbing...good luck πŸ‘

  • Thanks, Foggyme . I think I'll have to try and be more patient (and stop Googling my symptoms!).

  • Hi Foggyme , @taka, @Gambit62 and others. I've just had the results of Friday's blood tests back (the IFA test is not back yet, but I had that shortly after my B12 injection so I don't know if that will be particularly informative anyway). As you can see, my ESR has come down from 30mm to 11mm, I am low on Ferritin and Vitamin D deficient - does this suggest an absorption problem? Could this be related to B12 deficiency? I am feeling a lot better with very reduced neuro symptoms (touch wood) after having 8 x B12 injections with a few more in the pipeline. I would be really grateful for any feedback.


    Serum C reactive protein level < 4 mg/L [0.0 - 6.0]


    Erythrocyte sedimentation rate 11 mm [3.0 - 9.0]

    Above high reference limit

    Full blood count

    Total white blood count 4.7 10*9/L [3.9 - 10.2]

    Red blood cell count 5.00 10*12/L [3.9 - 5.2]

    Haemoglobin concentration 126 g/L [120.0 - 156.0]

    Haematocrit 0.396 L/L [0.355 - 0.455]

    Mean cell volume 79.6 fL [80.0 - 99.0]

    Below low reference limit

    Mean cell haemoglobin level 25.4 pg [27.0 - 33.5]

    Below low reference limit

    Red blood cell distribution width 14.5 % [11.0 - 16.0]

    Platelet count - observation 269 10*9/L [150.0 - 370.0]

    Plateletcrit 0.210

    Mean platelet volume 7.9 fL

    Neutrophil count 2.28 10*9/L [1.5 - 7.7]

    Lymphocyte count 1.89 10*9/L [1.1 - 4.5]

    Monocyte count - observation 0.26 10*9/L [0.1 - 0.9]

    Eosinophil count - observation 0.12 10*9/L [0.02 - 0.5]

    Basophil count 0.05 10*9/L [0.0 - 0.2]


    Serum magnesium level 0.85 mmol/L [0.7 - 1.0]


    Serum C reactive protein level < 4 mg/L [0.0 - 6.0]

    Serum ferritin level 7.5 ug/L [10.0 - 291.0]

    Below low reference limit

    Ferritin rises to an unpredictable extent with the acute phase

    response. If CRP is over 30 mg/L, the ferritin result may be high and



    Serum total 25-hydroxy vitamin D level 22.6 nmol/l

    ***Please note change of 25-OH vitamin D method with effect from


    Ranges below relate to TOTAL 25-OH Vitamin D

    Below 30 nmol/L is deficient

    30 - 50 nmol/L: may be inadequate in some people

    Above 50 nmol/L: is sufficient for almost the whole population

    There is some evidence that levels nearer 75 nmol/L may be beneficial

    for the frail elderly at risk of falling (see CUH Trust Guideline)

    Above 500 nmol/L: Toxicity likely

    For advice on management please see NOS publication :

    Vitamin D and Bone Health: A Practical Clinical Guideline

    for Patient Management and/or CUH Trust guidelines Ca

    and Vitamin D supplements to adults with GFR>30mL/min/1.73m2

    Thyroid function test

    Serum TSH level 3.67 mU/L [0.35 - 5.5]

    Serum free T4 level 12.7 pmol/L [10.0 - 19.8]


    Serum folate level 10.85 ug/L [> 5.38]

    Serum Folate Reference Range = Greater than 5.38 ug/L If the patient

    cannot be fasted be aware that a folate rich meal, eaten less than 3

    hours prior to venesection, may increase serum folate concentrations.

  • taka and Foggyme - do you think I should start a new post for my message above? I'm not sure about the protocol.

  • Hi rebs48. Yes...a new post is always best for 'new' things.

    The only reason I saw your post was because you tagged my name...if you reply to an old string (as here) it will only be seen by the person you are actually replying to (and those tagged in the message) or by anyone who happens to follow the post.

    None of our lovely forum members will spot you...and oh...all that lost advice πŸ˜–πŸ˜„


  • I'll upload it as a new post then! I would appreciate your wise advice though... :)

  • No problem...will take a peek...but may not be for a few hours...have to dodge of and do some 'stuff' πŸ‘

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